Biomedical subjects
Publications and source records attributed to P Graw.
The classic melancholic pattern of depressive symptoms being worse in the morning was present in 3/4 of a sample of 47 seasonal affective disorder patients (SAD), as assessed by global ratings and self-ratings of diurnal variation (DV). The type of DV did not predict response to light, but it did predict relapse within a week: Only those SAD patients with symptoms worse in the evening or no DV did so.
Melatonin, at the same doses used to treat circadian-rhythm related sleep disturbances, had no effect on the depressive symptoms in seasonal affective disorder (SAD) patients, whether given early (7 a.m.) or late (11 p.m.) for a week. Slight improvements in sleep were seen with nighttime administration. The circadian rhythmicity of urinary 6-sulphatoxymelatonin was not modified in any way. Melatonin at this dosage (5 mg/day) or at these two times is therefore not a potential alternative treatment for SAD; light remains the therapy of choice.
Seasonal affective disorder (SAD) patients often crave carbohydrates when depressed during the winter. We measured dietary intake using a daily Food/Drink Frequency Questionnaire in 36 SAD patients over four conditions: when depressed in winter, during light therapy (1 h 2500 lux, morning or evening), during withdrawal, and when euthymic in summer. Carbohydrate intake (both sweet and starch) in the second half of the day was elevated during winter depression and was as low after light therapy as in summer. The medial hypothalamus is hypothesised to play a key role in coupling 'mood and food' in SAD.
A sample of opiate addicts from the Basle area followed over six years (1979-1985) was in 1985 investigated concerning psychopathological features. Using the Derogatis scale significant differences between opiate abstinence and opiate dependence could be demonstrated. People still using opiates described themselves as being more obsessive, insecure, depressed, aggressive and anxious than people who had become abstinent from opiates. Patients in methadone maintenance were located in between. There were in addition significant differences between people living outside an institution and people being treated in therapeutic or penal institutions, but no differences between people from each kind of institution.
Bright white full spectrum light (greater than 2500 lux) can improve depressive symptomatology in a selected group of patients with recurrent autumn and winter depression. This crossover study demonstrates that 0.5-h morning white light is not an effective treatment, whereas 2-h is.
Drug addicts of the Basle area have been analysed during 6 years in connexion with the National Research Programme 'social integration' and also a following project. The results are contradictory to the pessimism which exists against changes of development of drug addicts.
Explore the source record for details and available documents.
Seasonal Affective Disorder (SAD) has been characterised by two or more depressive episodes in autumn or winter (with remission the following spring or summer), decreased energy, increased sleep, increased appetite, weight gain and carbohydrate craving. SAD patients were identified in a Swiss-German population; 22 participated in a light-therapy protocol (1 week bright white light 2,500 lux or dim yellow light 250 lux, from 06-08 h and 18-20 h). Both observer and self-ratings indicated a significant diminution of depressive symptoms with both lights. One week after withdrawal from yellow light, depression ratings relapsed to previous values; remission lasted longer after bright white light. Global VAS self-rating scales for "mood" and "well-being" however, and the Hamilton scale for atypical SAD symptoms, differentiated clearly between bright and dim light: only bright light showed an improvement that persisted after withdrawal. These results suggest that even though a placebo effect cannot be excluded, 4 h explicit light exposure/day may not be a negligible quantity. Light treatment promises to be a useful non-pharmacological intervention in certain forms of depressive illness.
Explore the source record for details and available documents.
In a first study we developed a test (BDA) for measuring the degree of dependence on alcohol, medicaments and drugs in alcoholics as well as drug addicts. The present study analysed this test according to the principles of construct validity. The aim was to create a test with those items that optimally fulfil some of the following criteria. This was achieved with 22 out of the original 59 items of the test. The shortened test contains those items that optimally differentiate both externally (the addicted population from the rest of the sample: depressives, neurotics and normals) and internally (the degree of dependence). The score obtained with 22 items was more efficacious in differentiating the addicts from the rest of the sample than the total score of 59 items. 86% of the 22 items are sufficiently sensitive to measure changes during hospitalisation in a psychiatric clinic. However only 33% of the 22 items can effectively discriminate between alcohol-, medicaments- und drug-dependence. Intercorrelation and factor analyses with other variables that were also measured indicate that a large part of the variance arises from unspecific "general psychopathology" and only a small part is specific for drug-dependence. The test is sufficiently reliable (rtt = .89), unifactoral, and with clear mean test-item correlation (rit = .54), to justify further investigation. We recommend this 22 items test for scientific research into dependence, in spite of the questions that still remain open. The English version of the 22 items is given in the appendix.
Forty hospitalized depressive patients of both sexes with primary depressive syndrome and concomitant diurnal variations were investigated at defined times with the following method: special questionnaire on subjective evaluation of depressive diurnal variation (TSF), mood scale (Bf-S of v. Zerssen), Necker cube, tests of autonomic function (amount of saliva and circulatory variables), global assessment of the depth of depression.--The quantitative differentiation into diurnal variations of different extents undertaken by means of the TSF were validated by the daily difference of the Bf-S. Between the extent of the depressive diurnal variation and the nosological group as well as the depth of depression no relationship could be found. Also the rate of turning over the Necker cube did not show any alteration in the diurnal rhythmicity. On the other hand, the inverse diurnal rhythmicity of the amount of saliva, also according to the corresponding results in the literature, can be interpreted as influence of the depressive diurnal variation. The resting values of pulse rate and blood pressure followed the diurnal physiological rhythm, but in addition they revealed a quantitative influence of the depressive diurnal variation (amplification). No systematic influences could be demonstrated for the orthostatic values.--The results show that in this methodological procedure only a few variables could be demonstrated to be associated with the depressive diurnal variation. On the other hand, it could be proved that not only mental but also certain autonomic components of the depressive syndrome undergo an alteration with the depressive diurnal variation.
Explore the source record for details and available documents.
Diurnal variations during the depressive phase and healthy periods were investigated in 84 hospitalised depressive patients of different nosological diagnosis. The occurrence of different rhythm-types in this population led to the conclusion that depression induces rhythmicity: those belonging to the arhythmic group when healthy showed significant increase in rhythmicity when depressed, predominantly the classical form of diurnal variation (morning with improvement toward evening). Age and sex were found to be important factors determining diurnal variation. In the course of hospitalisation, the type of diurnal rhythm remained individually constant.
Explore the source record for details and available documents.
Infusion of a new soluble ester of L-5-hydroxytryptophan produced euphoria in 34/35 experiments in healthy subjects. Parallel measurements of growth hormone and mood changes showed a similar rise and fall of these two parameters in 8/11 subjects. These results indicate that central stimulatory serotoninergic mechanisms (in addition to the well-known dopaminergic and alpha-adrenergic stimulation) play a role in the control of growth hormone release.
An i.v. injectable form of the serotonin-precursor L-5-hydroxytyptophan (Ro 3-5940) was investigated for its acute psychotropic effect. The difficulties are presented which had to be overcome as it was not known which effects could be expected. It was shown that for the intensive psychotropic effect found, it was not possible to use a long and detailed self-rating scale. The problem of informed consent is discussed.
L-5-hydroxytryptophan ethylester (Ro 3-5940), a new soluble form of this serotonin precursor, was administered to 26 healthy, non-depressed subjects after premedication with the peripheral decarboxylase inhibitor benserazide (Ro 4-6402) in a total of 51 infusions. Those conditions were chosen for the main trial which in a pre-trial investigation had proved to combine minimal side effects with clear central effects in particular the observed marked mood elevation after 1-5HTP. Using these standardized conditions of application, an interindividually similar pattern of the time course of substance effects could be shown, and convincing evidence was deducible for an objective mood elevating effect of 1-5HTP infusion. Amongst the most impressive results was the parallelity of the time course of mood changes and concomitant changes in serum growth hormone levels. Especially emphasized are the important questions of effectivity, specificity and clinical practicability or safety, which are essential for any precursor study. Arguments are presented supporting the assumption that primarily serotoninergic changes underlie these mood effects. In our opinion this mode of i.v. application of 1-5HTP represents a practicable strategy for investigating biochemical hypotheses as to serotonin mediated normal and deviant human behaviour, especially in affective disorders.
L-5HTP was found to act primarily on mood, and unequivocally in the direction of elation. The subjective, protocols, psychometric results, and a double-blind study demonstrated convincingly and intra-individually consistent course of action of the substance under the chosen conditions of application. This course of effects can be described in three phases: In a first phase (about 0 to 1 1/2 hours after end of infusion) an intensive mood elevation (mostly experienced as a disharmonious feeling), psychomotoric activity, changed perception, as well as somatic side effects were observed. A second phase (about 1 1/2 to 3 1/2 hours after end of infusion) was characterized by elevated mood (feeling of well-being) together with a tendency to inactivity, whereas other phenomena were less often reported. A third phase (about 3 1/2 to 6 hours after end of infusion) was characterized by mood decline and the feeling of having again reached "normality". Side effects again tended to occur. It is shown that neither placebo nor situative effects greatly influenced elevation of mood or other substance effects. This is demonstrated by the homogenous time course and the blind studies.